LETTER TO THE EDITOR Analyzing the Influence of Blood Loss on Outcomes of Cancer Surgery To the Editor:
of cancer surgery. Life expectancy is relatively short irrespective of tumor recurrence in patients older than 75 years. To elucidate the true effects of blood loss and blood transfusion on cancer-specific mortality, it would be necessary to construct further statistical models.
O
n the basis of multivariate analysis of the prospectively collected data from 3062 patients, M¨orner and colleagues1 concluded that blood loss of more than 250 mL during surgery was an independent risk factor of 5-year mortality after colon cancer surgery. In the Cox proportional hazard model, the primary outcome was all-cause mortality and the explanatory variables were age, sex, blood loss, stage of the disease, and postoperative complications (model 1) or blood transfusion (model 2). In model 2, blood transfusion was not an independent risk factor of 5-year mortality, whereas in model 1, age of 75 years or more was the strongest predictor for death. In dichotomizing the continuous data, a volume of 250 mL was chosen as a cutoff for blood loss because this was the median value for the whole group, whereas the reason for choosing 75 years as a cutoff age was unclear. These findings address questions of whether covariate selection and dichotomization of continuous data were appropriate and why moderate blood loss rather than blood transfusion was the predictor for death, because it is assumed that blood transfusion was required when blood loss was much more than 250 mL in the majority of patients transfused. In dichotomization of continuous variables, it seems reasonable to select a single cutoff point that maximizes significance but preserves clinical utility by univariate analysis. Using such methods, we identified blood loss of more than 500 mL as the most important predictor for major complications after total gastrectomy for gastric cancer2 and blood loss of more than 1200 mL as the most important risk factor for postoperative pneumonia after major abdominal surgery.3 Age at diagnosis is a factor that influences all-cause mortality and disease-specific mortality after cancer surgery.4 The age of 75 years, which is higher than median age of the study cohort, may not be adequate as a cutoff in assessing the effects of blood loss and blood transfusion on the long-term outcome
Reply: hank you for the opportunity to respond to the interesting letter from Dr Fujita. The aim of our study was to analyze the impact of blood lost during surgery for colon cancer on overall survival.1 Therefore, we chose the median volume of blood lost (250 mL) as a cutoff in the logistic regression analyses. A volume of blood lost less than 250 mL is possible to achieve during most surgeries for colon cancer. Blood transfusion can be given because of a large volume of blood lost during surgery and/or preoperative anemia. In a patient without preoperative anemia, blood would probably not be transfused due to a blood loss of 250 mL. It is difficult to separate the effects of bleeding and transfusion on survival. However, by choosing this rather low volume of blood lost, it is more likely that the effect is relatively more related to bleeding than to transfusion. To analyze the latter was not the aim of our study. Since the volume of bleeding is not normally distributed, it seems less wise to use it as a continuous variable. Still, blood loss is
Disclosure: The author declares no conflicts of interest. C 2014 Wolters Kluwer Health, Inc. All Copyright rights reserved. ISSN: 0003-4932/14/26103-e0070 DOI: 10.1097/SLA.0000000000000518
Disclosure: No conflicts of interest have been reported. The study received financial support from the Karolinska Institute, Stockholm County Council (ALF, grant number 20100123), and the Bengt Ihre Foundation. DOI: 10.1097/SLA.0000000000000519
e70 | www.annalsofsurgery.com
Tetsuji Fujita, MD Department of Surgery Jikei University School of Medicine Tokyo, Japan [email protected]
REFERENCES 1. M¨orner ME, Gunnarsson U, Jsetin P, et al. The importance of blood loss during colon cancer surgery for long-term survival an epidemiological study based on a population-based register. Ann Surg. 2012;255:1126–1128. 2. Fujita T, Yamazaki Y. Influence of surgeon’s volume on early outcome after total gastrectomy. Eur J Surg. 2002;168:535–538. 3. Fujita T, Sakurai K. Multivariate analysis of risk factors for postoperative pneumonia. Am J Surg. 1995;169:304–307. 4. Biau DJ, Porcher R. Breast cancer mortality and age at diagnosis. JAMA. 2012;307:2023.
T
a significant predictor for impaired survival also when blood loss is analyzed as a continuous variable with hazard ratio = 1.000152 (1.000037–1.000268). An age of 75 was chosen since it was close to the median in the material, 73.8 years (range 11.7–97.5), and has been used in other studies.2,3 The relationship between age and 5-year overall survival is not linear (ie, for instance, the difference in reduction between the years 50 and 55 is not equal to that of 80 to 85). However, recalculation of hazard ratios for impaired overall survival with age as a continuous variable showed the following hazard ratios: 1.05 (1.05–1.06) for age and 1.10 (1.00–1.22) for bleeding above median. We agree that there are several possible views for calculation and interpretation of the relationship between age, bleeding, and survival, most of them based on reliable arguments. Results from the present study, however, remained stable regardless of assumptions behind the analysis. We hope that the results of our study will encourage surgeons to put further efforts into minimizing blood loss during surgery for colon cancer. Malin E. M. M¨orner, MD Ulf Gunnarsson, PhD Monika Egenvall, PhD Division of Surgery Department for Clinical Science Intervention and Technology Karolinska Institutet Karolinska University Hospital Stockholm, Sweden [email protected]
REFERENCES 1. Morner ME, Gunnarsson U, Jestin P, et al. The importance of blood loss during colon cancer surgery for long-term survival: an epidemiological study based on a population based register. Ann Surg. 2012;255:1126–1128. 2. Schiffmann L, Ozcan S, Schwarz F, et al. Colorectal cancer in the elderly: surgical treatment and long-term survival. Int J Colorectal Dis. 2008;23: 601–610. 3. Tan E, Tilney H, Thompson M, et al., Association of Coloproctology of Great B. The United Kingdom National Bowel Cancer Project—epidemiology and surgical risk in the elderly. Eur J Cancer. 2007;43:2285–2294.
Annals of Surgery r Volume 261, Number 3, March 2015
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
of cancer surgery. Life expectancy is relatively short irrespective of tumor recurrence in patients older than 75 years. To elucidate the true effects of blood loss and blood transfusion on cancer-specific mortality, it would be necessary to construct further statistical models.
O
n the basis of multivariate analysis of the prospectively collected data from 3062 patients, M¨orner and colleagues1 concluded that blood loss of more than 250 mL during surgery was an independent risk factor of 5-year mortality after colon cancer surgery. In the Cox proportional hazard model, the primary outcome was all-cause mortality and the explanatory variables were age, sex, blood loss, stage of the disease, and postoperative complications (model 1) or blood transfusion (model 2). In model 2, blood transfusion was not an independent risk factor of 5-year mortality, whereas in model 1, age of 75 years or more was the strongest predictor for death. In dichotomizing the continuous data, a volume of 250 mL was chosen as a cutoff for blood loss because this was the median value for the whole group, whereas the reason for choosing 75 years as a cutoff age was unclear. These findings address questions of whether covariate selection and dichotomization of continuous data were appropriate and why moderate blood loss rather than blood transfusion was the predictor for death, because it is assumed that blood transfusion was required when blood loss was much more than 250 mL in the majority of patients transfused. In dichotomization of continuous variables, it seems reasonable to select a single cutoff point that maximizes significance but preserves clinical utility by univariate analysis. Using such methods, we identified blood loss of more than 500 mL as the most important predictor for major complications after total gastrectomy for gastric cancer2 and blood loss of more than 1200 mL as the most important risk factor for postoperative pneumonia after major abdominal surgery.3 Age at diagnosis is a factor that influences all-cause mortality and disease-specific mortality after cancer surgery.4 The age of 75 years, which is higher than median age of the study cohort, may not be adequate as a cutoff in assessing the effects of blood loss and blood transfusion on the long-term outcome
Reply: hank you for the opportunity to respond to the interesting letter from Dr Fujita. The aim of our study was to analyze the impact of blood lost during surgery for colon cancer on overall survival.1 Therefore, we chose the median volume of blood lost (250 mL) as a cutoff in the logistic regression analyses. A volume of blood lost less than 250 mL is possible to achieve during most surgeries for colon cancer. Blood transfusion can be given because of a large volume of blood lost during surgery and/or preoperative anemia. In a patient without preoperative anemia, blood would probably not be transfused due to a blood loss of 250 mL. It is difficult to separate the effects of bleeding and transfusion on survival. However, by choosing this rather low volume of blood lost, it is more likely that the effect is relatively more related to bleeding than to transfusion. To analyze the latter was not the aim of our study. Since the volume of bleeding is not normally distributed, it seems less wise to use it as a continuous variable. Still, blood loss is
Disclosure: The author declares no conflicts of interest. C 2014 Wolters Kluwer Health, Inc. All Copyright rights reserved. ISSN: 0003-4932/14/26103-e0070 DOI: 10.1097/SLA.0000000000000518
Disclosure: No conflicts of interest have been reported. The study received financial support from the Karolinska Institute, Stockholm County Council (ALF, grant number 20100123), and the Bengt Ihre Foundation. DOI: 10.1097/SLA.0000000000000519
e70 | www.annalsofsurgery.com
Tetsuji Fujita, MD Department of Surgery Jikei University School of Medicine Tokyo, Japan [email protected]
REFERENCES 1. M¨orner ME, Gunnarsson U, Jsetin P, et al. The importance of blood loss during colon cancer surgery for long-term survival an epidemiological study based on a population-based register. Ann Surg. 2012;255:1126–1128. 2. Fujita T, Yamazaki Y. Influence of surgeon’s volume on early outcome after total gastrectomy. Eur J Surg. 2002;168:535–538. 3. Fujita T, Sakurai K. Multivariate analysis of risk factors for postoperative pneumonia. Am J Surg. 1995;169:304–307. 4. Biau DJ, Porcher R. Breast cancer mortality and age at diagnosis. JAMA. 2012;307:2023.
T
a significant predictor for impaired survival also when blood loss is analyzed as a continuous variable with hazard ratio = 1.000152 (1.000037–1.000268). An age of 75 was chosen since it was close to the median in the material, 73.8 years (range 11.7–97.5), and has been used in other studies.2,3 The relationship between age and 5-year overall survival is not linear (ie, for instance, the difference in reduction between the years 50 and 55 is not equal to that of 80 to 85). However, recalculation of hazard ratios for impaired overall survival with age as a continuous variable showed the following hazard ratios: 1.05 (1.05–1.06) for age and 1.10 (1.00–1.22) for bleeding above median. We agree that there are several possible views for calculation and interpretation of the relationship between age, bleeding, and survival, most of them based on reliable arguments. Results from the present study, however, remained stable regardless of assumptions behind the analysis. We hope that the results of our study will encourage surgeons to put further efforts into minimizing blood loss during surgery for colon cancer. Malin E. M. M¨orner, MD Ulf Gunnarsson, PhD Monika Egenvall, PhD Division of Surgery Department for Clinical Science Intervention and Technology Karolinska Institutet Karolinska University Hospital Stockholm, Sweden [email protected]
REFERENCES 1. Morner ME, Gunnarsson U, Jestin P, et al. The importance of blood loss during colon cancer surgery for long-term survival: an epidemiological study based on a population based register. Ann Surg. 2012;255:1126–1128. 2. Schiffmann L, Ozcan S, Schwarz F, et al. Colorectal cancer in the elderly: surgical treatment and long-term survival. Int J Colorectal Dis. 2008;23: 601–610. 3. Tan E, Tilney H, Thompson M, et al., Association of Coloproctology of Great B. The United Kingdom National Bowel Cancer Project—epidemiology and surgical risk in the elderly. Eur J Cancer. 2007;43:2285–2294.
Annals of Surgery r Volume 261, Number 3, March 2015
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
